Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019

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Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
Leading a New Paradigm in
Cardiovascular Health Management
Jefferies 2019 Healthcare Conference
June 6, 2019
NASDAQ: AMRN
Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
Forward-Looking Statements and Disclaimer

Forward-looking statements
  This presentation contains forward-looking statements, such as those relating to the
  commercial potential of Vascepa®, clinical and regulatory efforts and timelines, potential
  FDA approvals, intellectual property, cash flow, and other statements that are predictive
  in nature and that depend upon or refer to future events or conditions, including financial
  guidance and milestones. These statements involve known and unknown risks,
  uncertainties and other factors that can cause actual results to differ materially. For
  example, as with any study result, further REDUCE-IT™ data assessment and data release
  by Amarin and FDA could yield additional useful information to inform greater
  understanding of the trial outcome. Investors should not place undue reliance on primary
  data or forward-looking statements, which speak only as of the presentation date of this
  presentation. Please refer to the “Risk Factors” section in Amarin’s most recent Form 10-Q
  filed with the SEC and cautionary statements outlined in recent press releases for more
  complete descriptions of risks in an investment in Amarin.

Presentation is for investors (not drug promotion)
  This presentation is intended for communication with investors only.
  Nothing in this presentation should be construed as promoting the use of Amarin’s
  product or product candidates.

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Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
Amarin Addressing Large Unmet Medical Needs

Problem: cardiovascular (CV) disease is an enormous and worsening
public health burden
Unmet Need: urgent need to help more patients with CV disease; lowering
cholesterol alone is not enough
               Solution: Landmark positive CV outcomes trial results of Amarin’s Vascepa®
               shows it can effectively and safely lessen this enormous CV health burden
                 Landmark global outcomes study positions Vascepa to become first drug to cost-
                  effectively help address residual CV risk beyond cholesterol management
                     ̶   Unprecedented results presented at AHA and published in NEJM in Nov’18
                 Amarin pursuing expanded label and promotion for Vascepa based on recent
                  outcomes study results from REDUCE-IT™ trial and sNDA submission
Current Label: Vascepa is already approved for important niche market of treating patients
with very high triglyceride levels >500 mg/dL
Advantage of Being First but Not New: potential cost-effective high share of voice coupled with
existing broad formulary coverage positions Vascepa well for growth in billion dollar market

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Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
Recent Highlights

sNDA for expanded REDUCE-IT indication accepted by FDA with priority review
   PDUFA date of September 28, 2019
   Accelerating plans for commercial expansion and launch following assumed FDA approval of Vascepa
        as the first therapy for its targeted CV risk reduction indication

67% increase in net total revenue in Q1 2019 compared to Q1 2018
   Growth primarily driven by increased volume of Vascepa sales
          ̶    Increased Vascepa prescription volume from prior prescribers and new prescribers
          ̶    NRx increase of ~80%, per Symphony Health, in Q1 2019 compared to Q1 2018

American Diabetes Association’s Standards of Medical Care updated to reflect REDUCE-IT results
   Recommendation added that icosapent ethyl be considered for patients with diabetes and
     atherosclerotic cardiovascular disease or other cardiac risk factors on a statin with controlled LDL-C, but
     with elevated triglycerides (135-499 mg/dL) to reduce CV risk

 1) Bhatt DL, Steg PG, Miller M, et al. Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT. J Am Coll Cardiol 2019. epub ahead of print.
    https://doi.org/10.1016/j.jacc.2019.02.032.
                                                                                                                                                            4
Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
Large Need for CV Risk Reduction Beyond Controlled LDL-C

                                                                                                                                                                        CV Risk
 ~65%-75% residual CV risk beyond current standard of care1
    Controlled LDL-C does not eliminate CV risk
    Remaining residual CV risk high even with controlled LDL-C                                                                                             LDL-C
                                                                                                                                                            control
                                                                                                                                                            25-35%
 Cardiovascular Disease: #1 cause of death in the U.S.
    >800,000 deaths each year attributable to CV disease;
                                                                                                                                                                            Residual
     more than all cancers combined2                                                                                                                                        Risk/Unmet Need
    Annual treatment cost $555 billion; expected to double                                                                                                                 65-75%
     within twenty years3, 4
    One death every 38 seconds

   No FDA approved therapy exists for treating CV risk in dyslipidemia patients beyond LDL-C
     ~38M patients in U.S. are on statin therapy
     >25% of adults in U.S. have CV risk factors beyond LDL-C (e.g. ~50M to 70M adults in U.S.
      have elevated triglycerides levels >150 mg/dL)
                   ̶    ~12M of these patients are already on statin therapy

1) Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE. Unmet need for adjunctive dyslipidemia therapy in hypertriglyderidemia management. J Am Coll Cardiol. 2018. 2) AHA: Heart Disease and Stroke Statistics 2018
At-a-Glance 3) http://www.heart.org/idc/groups/heart-public/@wcm/@adv/documents/downloadable/ucm_491543.pdf 4) Centers for Disease Control and Prevention, https://www.cdc.gov/nchs/fastats/leading-
causes-of-death AHA: Cardiovascular Disease: A Costly Burden for America — Projections through 2035.htm, January, 20, 2017,
                                                                                                                                                                                                             5
Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
CV Risk Increases Across TG Levels up to ~150 mg/dL
  Above Which Risk Remains but the Relationship Flattens

                           15%

                                                                                                                               Dashed lines reflect
                                                                                                                               95% confidence interval
       Predicted CV Risk

                           10%

                                                                                                                               In addition to this clinical
                                                                                                                               data, genetics studies
                           5%                                                                                                  support that TG levels
                                                       CV risk begins increasing                                               are as well correlated to
                                                       at TG levels
Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
Unprecedented CV Outcomes Position Amarin for Growth

REDUCE-IT cardiovascular outcomes study was robustly conducted
  Evaluated Vascepa effects on statin-treated patients with residual elevated TG and other CV risks
    ̶ Patients had well-controlled baseline LDL-C (median 75 mg/dL) and remained on statin therapy
         and other standard of care medications
      ̶ 8,179 patients randomized 1:1 between Vascepa-arm and placebo-arm
    Conducted under a Special Protocol Assessment (SPA) agreement with FDA
    >35,000 patient years of study
REDUCE-IT results were positive as per peer reviewed presentations and publications
  Primary results based on first occurrence of major adverse cardiovascular events (MACE):
      ̶   Presented at AHA scientific sessions in Nov 2018
      ̶   Published in The New England Journal of Medicine (NEJM); the NEJM Journal Watch Cardiology and the
          American College of Cardiology recognized REDUCE-IT results as top cardiovascular news for 2018
  Total events based on first and recurrent MACE:
      ̶   Presented at ACC scientific sessions in Mar 2019
      ̶   Published in Journal of American College of Cardiology

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Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
Primary Endpoint Achieved in Vascepa Outcomes Study
Largest CV Risk Reduction of Any Drug on Top of Statin Therapy

Endpoint                                            Relative Risk Reduction (RRR)                           P-value
                                                       on top of statin therapy

Primary Endpoint (5-point MACE)                                       ↓ 25%                              0.00000001

Key Secondary Endpoint (3-point “Hard” MACE) ↓ 26%                                                       0.0000006

CV Death                                                              ↓ 20%                                    0.03

Heart Attack (Fatal or Nonfatal)                                      ↓ 31%                                0.000005

Stroke (Fatal or Nonfatal)                                            ↓ 28%                                    0.01

  “This may be the biggest development in cardiovascular prevention since statins.”
         - Deepak L. Bhatt, MD, MPH
              Professor of Medicine at Harvard Medical School
              Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital Heart and Vascular Center
              Global Principal Investigator and Steering Committee Chair for REDUCE-IT
              - Brigham and Women’s REDUCE-IT results press release November 10, 2018

    MACE = major adverse cardiovascular events

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Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
CV Event Curve for Primary Endpoint Separated at ~1 Year
  and Remained Separated Throughout Follow-up Period

                                     30
                                                                                  28.3%

                                                                                                 Hazard Ratio, 0.75
        Patients with an Event (%)

                                     20                                                          (95% CI, 0.68–0.83)
                                                      Placebo
                                                                                         23.0%   RRR = 24.8%
                                                                                                 ARR = 4.8%
                                                                                                 NNT = 21 (95% CI, 15–33)
                                                                    Vascepa (icosapent ethyl)
                                     10
                                                                                                 P=0.00000001

                                     0
                                          0   1   2             3            4            5

                                                  Years since Randomization

  CV event curve for key secondary endpoint (3-point MACE), not shown here, separated
  prior to 2 years and remained separated throughout follow-up period

Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2018.
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Leading a New Paradigm in Cardiovascular Health Management - Jefferies 2019 Healthcare Conference June 6, 2019
MACE Continues to be REDUCED Beyond 1st Events
      (25%, 32%, 31% and 48% for 1st, 2nd, 3rd and 4th Events, Respectively)

                                                                                                    RR 0.70                           30% Reduction in Total Events
                                                                                                (95% CI, 0.62-0.78)                   Average ~1 Fewer Event per 6 Patients
                                                                                              P=0.00000000036                         Treated with Icosapent Ethyl for 5 years
                                                                            1,546
                                                    1,600
                                                                                                   ≥4 Events
      Number of Primary Composite Endpoint Events

                                                                             126                                                                               No. of
                                                                                                    RR 0.52                                                    Fewer
                                                    1,400
                                                                             143               (95% CI, 0.38-0.70)                                             Events
                                                    1,200                                          3rd Events                  1,076                           -470
                                                                                                    HR 0.69
                                                                             376               (95% CI, 0.59-0.82)               63                             -63
                                                    1,000                                                                        72                             -71
                                                                                                   2nd Events
                                                     800                                            HR 0.68                     236                            -140
                                                                                               (95% CI, 0.60-0.78)
                                                     600
                                                                             901
                                                     400                                            1st Events
                                                                                                     HR 0.75                    705                            -196
                                                                                               (95% CI, 0.68-0.83)
                                                     200                                        P=0.000000016

                                                       0
                                                                           Placebo                                         Icosapent Ethyl
                                                                          [N=4090]                                            [N=4089]

                                                            Reduced Dataset Event No.   1st         2nd       3rd     ≥4                            RR= rate ratio
                                                                                                                                                    HR= hazard ratio

Bhatt DL, Steg PG, Miller M, et al. J Am Coll Cardiol. 2019.

                                                                                                                                                                         10
Total (First and Subsequent) Events
     Key Secondary Endpoint (3 Point “Hard” MACE: CV Death, MI, Stroke)

       Key Secondary Composite Endpoint

                                        0.3                                                      Total Events:
                                                  Placebo: Total Events
                                                                                                 RR, 0.72
                                                  Icosapent Ethyl: Total Events
       Cummulative Events per Patient

                                                                                                 (95% CI, 0.63–0.82)
                                                  Placebo: First Events
                                                  Icosapent Ethyl: First Events                  P=0.00000071
                                        0.2                                                          Primary (1st) Events:
                                                                                                     HR, 0.74
                                                                                                     (95% CI, 0.65–0.83)
                                                                                                     P=0.0000006

                                        0.1

                                        0.0
                                              0     1          2          3       4   5
                                                         Years since Randomization
                                                                                          RR= rate ratio
                                                                                          HR= hazard ratio
Bhatt DL, Steg PG, Miller M, et al. J Am Coll Cardiol. 2019.

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Additional Important Results from REDUCE-IT

                                                                                                                                                                            Vascepa®
     Positive results consistent across multiple subgroups including
                                                                                                                                                                          REDUCE-IT3
        Male/female                                                                                                                                                        2018
        Diabetes/no diabetes
        Secondary/primary prevention cohorts                                                                                                                                 20%
                                                                                                                                                                            CV Death3
     Number needed to treat (NNT): 21 for primary endpoint
        Low NNT combined with affordable price of Vascepa
         should support continued broad managed care coverage                                                                                                                25%
        For context, NNTs for other notable, but not competitive with                                                                                                    RRR MACE3
         Vascepa, drugs:
           ̶ Atorvastatin (Lipitor®)1: 45
            ̶ Evolocumab (Repatha®)2: 67
                • No head-to-head study with these drugs                                                                                                                         21             NNT3

                • Study periods and study populations differ

     ~1 fewer MACE per 6 patients treated in total event analysis4
        Result should be helpful in pharmacoeconomic analysis
1) LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352: 1425–35. 2) Sabatine MS, Giugliano RP, Keech AC, et al.
Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713. 3) Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2018. 4) Bhatt DL, Steg PG, Miller M, et al. Effects of Icosapent
Ethyl on Total Ischemic Events: From REDUCE-IT. J Am Coll Cardiol 2019. epub ahead of print. http://doi.org/10.1016/2019/03/01/j.jacc.2019.02.032

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Robust CV Risk Reduction Independent of TG Levels

  Reduction of CV events was similar for patients with TG levels above and below 150 mg/dL
     ~10% of patients enrolled had TG levels
Vascepa Well Tolerated with Safety Profile Consistent with
   Omega-3 Fatty Acids and Current FDA Labelling

Overall adverse event rates in REDUCE-IT were similar across the statin plus Vascepa and the
statin plus placebo treatment groups
       Overall patient population had numerous events reflecting their at-risk condition and need
         for medical care
       No significant differences between treatments in the overall rate of treatment-emergent
         adverse events or serious adverse events leading to withdrawal of study drug
No Serious Adverse Event (SAE) >2% frequency and greater in Vascepa-arm
Adverse Events (AE) greater in the Vascepa-arm, included:
   Peripheral edema (6.5% Vascepa-arm; 5.0% placebo-arm), atrial fibrillation (5.3% Vascepa-
    arm; 3.9% placebo-arm) and serious bleeding (2.7% Vascepa-arm; 2.1% placebo-arm)
   These events did not appear associated with increased MACE or other major issues
             ̶    Peripheral edema increased without increase in heart failure
             ̶    AFib increased but heart attack, cardiac arrest and sudden death each decreased >30%
             ̶    Bleeding rates were characterized as low; no fatal bleeding assessed by investigators as related
                  to Vascepa; no significant increases in hemorrhagic stroke, CNS bleeding or GI bleeding

Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2018.
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25% RRR on Top of Controlled LDL-C is Landmark Result

                                                 Relative Risk     Positive         Peak Net
                Class                CVOT
                                                Reduction (RRR)     CVOT           Sales in U.S.
STATIN THERAPY
 Statins                            Various         25-35%             √           >$20B - 2016
OTHER LDL-CHOLESTEROL LOWERING DRUGS ON TOP OF STATIN THERAPY
 Cholesterol Absorption Inhibitors IMPROVE-IT         6%               √           $1.8B - 2007
                                FOURIER              15%
 PCSK9 Inhibitors                                                      √        Recently Launched
                                ODYSSEY              15%
OTHER DRUGS ON TOP OF STATIN THERAPY
 Anti-Inflammatory                  CANTOS            15%              √               N/A
 Omega-3 Mixture (Lovaza 1g/d)   ASCEND/VITAL Not Significant         X            $1.0B - 2013
 EPA (Epadel)                         JELIS           19%              √        N/A (in Japan only)
 EPA (Vascepa)                     REDUCE-IT          25%              √               TBD

25% RRR with Vascepa is largest of any therapy on top of statins
Many other therapies failed trying to lower CV risk (e.g. CETP inhibitors, fibrates, niacin)
Lipitor (atorvastatin) lowers CV risk ~25%; REDUCE-IT effect is incremental to statins

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Science of Lipid Management and Clinical Effects of Omega-3
  Fatty Acids Are Complex

Vascepa is unique proven prescription therapy developed over 10 years at cost of >$500M
Single active ingredient EPA (eicosapentaenoic acid)
   Unique omega-3 molecule1 derived from nature
      ̶ New chemical entity designation by FDA for Vascepa as pure EPA
       ̶ Purity achieved while overcoming the fragility and stability issues associated with omega-3s
   Excludes saturated fats, omega-6s and other components in fish oil
   No known drug-drug interactions1
EPA is smaller than DHA in length and number of double bonds that influence activities
   Small molecule capable of entering and improving function of endothelial cells
   Doesn’t inhibit clearance of LDL-C like DHA (docosahexaenoic acid)
Omega-3s are easily oxidized or otherwise damaged
   Vascepa is expertly manufactured and encapsulated
   Demonstrated multi-year stability with consistent reproducibility

  1
  See Vascepa® {package insert}. Bedminster, NJ: Amarin Pharma Inc.; 2017
                                                                                                        16
Mechanistic Effects of Vascepa’s Active Ingredient on Multiple
   Atherosclerotic Processes Beyond Lipid Modification
                                                    Multiple Processes Potentially Affected by EPA1
                     Endothelial function                     Inflammation/cytokines    Plaque formation/progression
                     Oxidative stress                                                    Platelet aggregation
                     Foam cell formation                                                 Thrombus formation
                                                                                          Plaque rupture

   The extent to which these or other pleiotropic effects of EPA may have contributed to the success of
   Vascepa in the REDUCE-IT study relative to other effects of EPA (e.g. lipid lowering) is under evaluation

1. Borow KM et al. Atherosclerosis. 2015;242(1):357-366
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Commercial Expansion Aligns with Improved Patient Care

Priority focus on large U.S. market opportunity
Transforming from niche to large outcomes-based opportunity

Market experience provides foundation for growth
  Managed care coverage already broad
  >5M Rx for Vascepa since launched for niche market in 2013
Expanding Vascepa promotion in 2019
  Expanded U.S. physician targets from ~20k to >50k
  Initial feedback from healthcare professionals regarding REDUCE-IT
   results broadly positive with new prescribers increasing
  Targeted promotion based on Amarin’s First Amendment decision
   and related FDA agreement reached in 2016 regarding
   communication of truthful and non-misleading information to
   healthcare professionals
      ̶ Expand promotion further following label expansion
Vascepa promotion to expand further following label expansion
  Current promotion is qualified and limited, particularly to consumers

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Preparing for Growth

Strengthening relationships
  Building relationships with KOLs and industry groups
      ̶   24 scientific publications/posters supported in early 2019 and >40 in 2018
      ̶   Active in medical education programs and other forms of educational and promotional outreach
Supply capacity expanding
  Multiple proven suppliers for Vascepa
      ─ Evaluating options to expand capacity to support multiple billions of dollars in revenue
Sustainable business
  Vascepa patents listed in the FDA’s Orange Book expire in 2030
    ─ Teva, by agreement, may launch generic in August 2029
  NCE protection
International expansion
  Middle East: Partner obtained approved for Vascepa sales in Lebanon and United Arab Emirates with
     applications in other countries under review
    Canada: Partner received priority review from Health Canada for Vascepa; NDS seeking Vascepa label
     based on REDUCE-IT submitted to Health Canada on Apr 26, 2019
    China: Regulatory approval for Vascepa being pursued via ongoing clinical study
    Europe: Aiming before the end of 2019 to submit application seeking approval for Vascepa
    Other geographies: opportunities being pursued

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Evolution of Preventative Cardiovascular Care

Before statin therapy                                 Focus on LDL-C

                                                           STATINS
       Pre-Statins
                                                           PCSK9s
       Cholesterol                                        Ezetimibe
         Resins

    After statin therapy,                        ~25% RRR on top of statins
modification of other lipid markers
    have not lowered CV risk

        Fibrates,
                                                           VASCEPA®
         Niacin,
        Omega-3
        Mixtures

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Capitalization Summary (Millions)
As of March 31, 2019

      Cash and Cash Equivalents                                $211

      Debt Obligations

             NOTES                                              $ - None

             ROYALTY-BEARING INSTRUMENT1                        $81 10% of revenues until fully paid; no maturity date

      Common Stock and Equivalent Shares
             COMMON/PREFERRED SHARES2                           360 Preferred shares mirror common but non-voting

             OPTIONS AND RESTRICTED STOCK                        26

               TOTAL IF ALL EXERCISED                           386

      Tax Jurisdiction (primary)                             Ireland Loss carryforwards of ~$800

1 Representsface value of debt balance remaining to be paid in cash; a slightly lower carrying value is reported for accounting
 purposes in accordance with U.S. GAAP
2 Includes   29 million common share equivalents issuable upon conversion of preferred shares

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Leading a New Paradigm in
Cardiovascular Health Management
Jefferies 2019 Healthcare Conference
June 6, 2019
NASDAQ: AMRN
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